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Published on: August 23, 2024
SRPIN340 protects heart muscle from oxidative damage via SRPK1/2 inhibition-mediated AKT activation
Jian Huang1, Yaqun Zhou2, Xiaoyu Xue2
1Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Abstract:
SRPIN340, a selective serine-arginine protein kinase 1/2 (SRPK1/2) inhibitor, has been shown to have antiviral and anti-angiogenesis effects. However, its role in the heart is unknown. The present study explored the role of SRPIN340 in myocardial protection and the related mechanisms. During challenge with H2O2, cardiomyocytes (CMs) pretreated with SRPIN340 showed strikingly more injury tolerance, which was manifested as reduced lactate dehydrogenase (LDH) release and lower apoptotic index. Further research showed that SRPIN340 activated AKT under basal conditions, and AKT inhibition abolished the protective effects of SRPIN340 treatment during H2O2 stress. The protective effect of SRPIN340 was also demonstrated in perfused rat hearts subjected to ischemia/reperfusion (I/R). Collectively, our results reveal the beneficial effects of SRPIN340 against H2O2-induced oxidative damage in CMs and I/R-induced injury in a Langendorff heart model, supporting a potential application of SRPIN340 in the clinically relevant context of reperfusion. The effectiveness of SRPIN340 may be attributed to AKT signal activation.
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